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Endocrinol Metab 2015;30:233-234
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Expression of Glucagon-Like Peptide-1 Receptor in Papillary Thyroid Carcinoma and Its Clinicopathologic Significance
(Endocrinol Metab 2014;29:536-44, Min Jung Jung et al.)
Min Jung Jung1, Su Kyoung Kwon2
1Department of Pathology, 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
Thank you for your interest and comments on our article enti- tled “Expression of glucagon-like peptide-1 receptor in papil- lary thyroid carcinoma and its clinicopathologic significance,”
which was published in Endocrinology and Metabolism [1].
We reported the expression of the glucagon-like peptide-1 receptor (GLP-1R) in papillary thyroid carcinoma (PTC) tis- sues based on immunohistochemical (IHC) staining. However, we could not find a meaningful relationship between clinical prognostic markers and GLP-1R expression in PTC, but the less multifocality of GLP-1R expression in PTC tissues. These findings were unexpected and interesting because previous studies reported that GLP-1R is not expressed in thyroid fol- licular cells and GLP-1 plays a possible role in cell prolifera- tion and apoptosis in pancreatic β-cells.
IHC staining is well-established and used widely for identi- fying specific pathological processes, including protein ex- pression nevertheless, the pathologist’s interpretation is sub- jective. To convert the subjective perception of IHC marker expression into quantitative data, various semiquantitative scoring systems have been suggested. For example, in breast cancer, representative tumors were subjected to several IHC
stains, including estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67. Pathologists use the quickscore, modi- fied H-score, immunoreactive score and Allred score [2,3] as generally accepted standard interpretation guidelines for IHC staining of ER and PR. In Allred score, pathologists score the proportions of ER-positive immunoreactive cells into six cate- gories (0, no cells are ER-positive; 1, ≤1%; 2, 1% to 10%; 3, 11% to 33%; 4, 34% to 66%; and 5, 67% to 100% are ER-pos- itive) and intensity into four categories (0, negative; 1, weak;
2, intermediate; and 3, strong). The final score is the sum of these two scores, where the minimal standard hormone recep- tor-positive score is 3 and the mandatory minimum of tumor cells is 1% regardless of intensity. A similar approach was demonstrated in “quickscore,” modified H-score system, with the differences in values in proportion category A from 1 to 6 (1, 0% to 4%; 2, 5% to 9%; 3, 20% to 39%; 4, 40% to 59%; 5, 60% to 79%; and 6, 80% to 100%) and using multiplication for final scoring [2]. However, the generally accepted interpre- tation guideline for IHC staining of HER2 is different. Pathol- ogists evaluate the immunoreactive pattern (complete vs. in- complete circumferential membrane staining), intensity (none,
Received: 3 April 2015, Revised: 9 April 2015, Accepted: 21 May 2015
Corresponding author: Su Kyoung Kwon
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, 262 Gamcheon-ro, Seo-gu, Busan 602-702, Korea
Tel: +82-51-990-6102, Fax: +82-51-990-3077, E-mail: [email protected]
Copyright © 2015 Korean Endocrine Society
This is an Open Access article distributed under the terms of the Creative Com- mons Attribution Non-Commercial License (http://creativecommons.org/
licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribu- tion, and reproduction in any medium, provided the original work is properly cited.
Jung MJ, et al.
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www.e-enm.org Copyright © 2015 Korean Endocrine Societyweak, moderate, and intense), and proportion of immunoreac- tive cells (≤10%, >10%). The final interpretation is based on the combination of these three results [4]. In the general guide- line for interpreting the IHC staining for Ki67, pathologists evaluate only the proportion of immunoreactive cells (low, Ki67 index <14%; high, Ki67 index ≥14%) [5]. Furthermore, investigators have used various interpretation methods to compensate for the equivocal immunoreactivity with many IHC stains [6]. Even among researchers using quickscore, there are various interpretation methods and criteria based on the proportion and intensity scores, calculation method (addi- tion vs. multiplication), and what is interpreted as a positive immunoreaction. These differences in the IHC interpretation system are considered a major cause of discordant results among studies.
In our study, we interpreted the results of IHC staining us- ing both intensity and the proportion of GLP-1R immunoreac- tive cells. Negative immunoreactivity was defined as no stain- ing or ambiguous staining and strong immunoreactivity was defined as any cells with strong staining intensity regardless of the distribution. However, weak intensity was interpreted ac- cording to the distribution of immunoreactive cells in the en- tire tumor with a minimum cutoff value of 5%. This interpre- tation system focuses more on the intensity of stained cells compared to the breast tumor quickscore, in which the propor- tion of stained cells is more important. Our study is pioneering research on GLP-1R expression in PTC based on IHC expres- sion. Therefore, we focused on the existence of aberrant GLP- 1R expression in PTC, rather than the differences between ex- pressed or non-expressed GLP1-R in PTC or differences among various degrees of GLP-1R expressed in PTC. More- over, the distribution of GLP-1R immunoreactive cells was diffuse and spread over 50% of the entire tumor in all except two of 18 cases, which showed moderately intense immunore- activity in 20% of the tumor. Therefore, fine separation of im- munoreactive cell proportion is considered as less meaningful.
To date, there is insufficient information to determine the best interpretation method for GLP-1R expression in PTC. We hope to obtain more objective and validated results in future studies including a more quantitative scoring system for IHC staining, such as the quickscore method. We sincerely appreci- ate Park et al. for their interest in our study and knowledgeable
comments.
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was re- ported.
REFERENCES
1. Jung MJ, Kwon SK. Expression of glucagon-like peptide-1 re- ceptor in papillary thyroid carcinoma and its clinicopathologic significance. Endocrinol Metab (Seoul) 2014;29:536-44.
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